tbuckley/cabot-search huggingface dataset:
Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study
Authors: Melissa L. Johnson, Byoung Chul Cho, Alexander Luft, Jorge Alatorre-Alexander, Sarayut Lucien Geater, Konstantin Laktionov, Sang-We Kim, Grygorii Ursol, Maen Hussein, Farah Louise Lim, Cheng-Ta Yang, Luiz Henrique Araujo, Haruhiro Saito, Niels Reinmuth, Xiaojin Shi, Lynne Poole, Solange Peters, Edward B. Garon, Tony Mok
Journal: Journal of Clinical Oncology (2022)

PURPOSE The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non–small-cell lung cancer (mNSCLC). METHODS Patients (n = 1,013) with EGFR/ ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT. RESULTS PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events. CONCLUSION D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.
Abdominal aortic aneurysm monitoring via arterial waveform analysis: towards a convenient point-of-care device
Authors: Mohammad Yavarimanesh, Hao-Min Cheng, Chen-Huan Chen, Shih-Hsien Sung, Aman Mahajan, Rabih A. Chaer, Sanjeev G. Shroff, Jin-Oh Hahn, Ramakrishna Mukkamala
Journal: npj Digital Medicine (2022)

Abstract Abdominal aortic aneurysms (AAAs) are lethal but treatable yet substantially under-diagnosed and under-monitored. Hence, new AAA monitoring devices that are convenient in use and cost are needed. Our hypothesis is that analysis of arterial waveforms, which could be obtained with such a device, can provide information about AAA size. We aim to initially test this hypothesis via tonometric waveforms. We study noninvasive carotid and femoral blood pressure (BP) waveforms and reference image-based maximal aortic diameter measurements from 50 AAA patients as well as the two noninvasive BP waveforms from these patients after endovascular repair (EVAR) and from 50 comparable control patients. We develop linear regression models for predicting the maximal aortic diameter from waveform or non-waveform features. We evaluate the models in out-of-training data in terms of predicting the maximal aortic diameter value and changes induced by EVAR. The best model includes the carotid area ratio (diastolic area divided by systolic area) and normalized carotid-femoral pulse transit time ((age·diastolic BP)/(height/PTT)) as input features with positive model coefficients. This model is explainable based on the early, negative wave reflection in AAA and the Moens-Korteweg equation for relating PTT to vessel diameter. The predicted maximal aortic diameters yield receiver operating characteristic area under the curves of 0.83 ± 0.04 in classifying AAA versus control patients and 0.72 ± 0.04 in classifying AAA patients before versus after EVAR. These results are significantly better than a baseline model excluding waveform features as input. Our findings could potentially translate to convenient devices that serve as an adjunct to imaging.
Targeting UGCG Overcomes Resistance to Lysosomal Autophagy Inhibition
Authors: Vaibhav Jain, Sandra L. Harper, Amanda M. Versace, Dylan Fingerman, Gregory Schuyler Brown, Monika Bhardwaj, Mary Ann S. Crissey, Aaron R. Goldman, Gordon Ruthel, Qin Liu, Aleksandra Zivkovic, Holgar Stark, Meenhard Herlyn, Phyllis A. Gimotty, David W. Speicher, Ravi K. Amaravadi
Journal: Cancer Discovery (2022)

Lysosomal autophagy inhibition (LAI) with hydroxychloroquine or DC661 can enhance cancer therapy, but tumor regrowth is common. To elucidate LAI resistance, proteomics and immunoblotting demonstrated that LAI induced lipid metabolism enzymes in multiple cancer cell lines. Lipidomics showed that LAI increased cholesterol, sphingolipids, and glycosphingolipids. These changes were associated with striking levels of GM1+ membrane microdomains (GMM) in plasma membranes and lysosomes. Inhibition of cholesterol/sphingolipid metabolism proteins enhanced LAI cytotoxicity. Targeting UDP-glucose ceramide glucosyltransferase (UGCG) synergistically augmented LAI cytotoxicity. Although UGCG inhibition decreased LAI-induced GMM and augmented cell death, UGCG overexpression led to LAI resistance. Melanoma patients with high UGCG expression had significantly shorter disease-specific survival. The FDA-approved UGCG inhibitor eliglustat combined with LAI significantly inhibited tumor growth and improved survival in syngeneic tumors and a therapy-resistant patient-derived xenograft. These findings nominate UGCG as a new cancer target, and clinical trials testing UGCG inhibition in combination with LAI are warranted. We discovered UGCG-dependent lipid remodeling drives resistance to LAI. Targeting UGCG with a drug approved for a lysosomal storage disorder enhanced LAI antitumor activity without toxicity. LAI and UGCG inhibition could be tested clinically in multiple cancers. This article is highlighted in the In This Issue feature, p. 247.
Biomimicking Leaf‐Vein Engraved Soft and Elastic Membrane Promotes Vascular Reconstruction
Authors: Jinghan Fang, Huaqian Liu, Wei Qiao, Tianpeng Xu, Yuhe Yang, Huizhi Xie, Chun‐Hei Lam, Kelvin W. K. Yeung, Xin Zhao
Journal: Advanced Healthcare Materials (2022)

Hierarchical vasculature reconstruction is fundamental for tissue regeneration. The regeneration of functional vascular network requires a proper directional guidance, especially in case of large-size defects. To provide the "running track" for vasculature, a leaf-vein mimetic membrane using soft and elastic poly(lactide-co-propylene glycol-co-lactide) dimethacrylate is developed. Engraved with an interconnected and perfusable leaf-vein micropattern, the membrane can guide human umbilical vein endothelial cells (HUVECs) to form vasculature in vitro. In particular, the "running track" upregulates the angiogenesis-related gene expression and promotes the HUVECs to differentiate into tip cells and stalk cells via tuning vascular endothelial growth factor receptor 2 signaling transduction. As a proof of concept, its revascularization capability using a rat calvarial defect model in vivo is evaluated. The in vivo results demonstrate that the leaf-vein engraved membrane accelerates the formation and maturation of vasculature, leading to a hierarchical blood vessel network. With the superior pro-vasculature property, it is believed that the leaf-vein engraved membrane is not only an ideal candidate for the reconstruction of calvarial vasculature but also a promising solution for more complicated vasculature reconstruction, such as muscle, skin, and heart.
Relugolix/Estradiol/Norethisterone (Norethindrone) Acetate: A Review in Symptomatic Uterine Fibroids
Authors: Yahiya Y. Syed
Journal: Drugs (2022)

An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU. Relugolix is a gonadotropin releasing hormone (GnRH) receptor antagonist that decreases serum estradiol and progesterone concentrations to postmenopausal levels. The addition of estradiol/norethisterone acetate to relugolix ameliorates relugolix-induced bone loss and hot flush. In the two phase 3 LIBERTY trials, relugolix + estradiol/norethisterone substantially decreased menstrual bleeding and improved a range of other uterine fibroid symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated, with vasomotor symptoms being the most common adverse reaction. Treatment with this combination for over up to 2 years did not induce a clinically meaningful bone loss in the majority of women. Relugolix/estradiol/norethisterone acetate, with its convenient once-daily administration, is a useful addition to current pharmacological treatment options for premenopausal women with symptomatic uterine fibroids. Uterine fibroids are a common type of noncancerous tumours that grow in the uterus. In some women, these tumours cause debilitating symptoms, such as heavy menstrual bleeding, pelvic pain and passing of blood clots. Hysterectomy is the only definitive treatment for this condition, but is associated with some disadvantages. Less invasive procedures and medical treatments are now available to treat these symptoms. Recently, a fixed-dose tablet comprising relugolix, estradiol and norethisterone acetate (Ryeqo®; Myfembree®) has been approved to treat symptoms of uterine fibroids. This combination works by suppressing ovarian hormone levels. In clinical trials, relugolix + estradiol/norethisterone substantially reduced menstrual bleeding and improved several other symptoms in women with uterine fibroids-associated heavy menstrual bleeding. The combination was generally well tolerated and had a minimal impact on bone loss, a known adverse effect of such therapies. With its convenient once-daily administration, relugolix/estradiol/norethisterone acetate is a useful addition to current medical treatment options for premenopausal women with symptomatic uterine fibroids.
Emerging Technologies Used in Health Management and Efficiency Improvement During Different Contact Tracing Phases Against COVID-19 Pandemic
Authors: Maggie Ezzat Gaber Gendy, Mehmet Rasit Yuce
Journal: IEEE Reviews in Biomedical Engineering (2022)

Confronted with the COVID-19 health crisis, the year 2020 represented a turning point for the entire world. It paved the way for health-care systems to reaffirm their foundations by using different technologies such as sensors, wearables, mobile applications, drones, robots, Artificial Intelligence (AI), Machine Learning (ML) and the Internet of Things (IoT). A lot of domains have been renovated such as diagnosis, treatment, and monitoring, as well as previously unprecedented domains such as contact tracing. Contact tracing, in conjunction with the emergence, spread, and public compliance for vaccines, was a critical step for controlling and limiting the spread of the pandemic. Traditional contact tracing is usually dependent on individuals ability to recall their interactions, which is challenging and yet not effective. Consequently, further development and usage of automated, privacy-preserving, digital contact-tracing was required. As the pandemic is coming to an end, it is vital to collect and learn the effective used technologies that aided in fighting the virus in order to be prepared for any future pandemics and to be aware of any literature gaps that must be filled. This paper surveys state-of-the-art architectures, platforms, and applications combating COVID-19 at each phase of the five basic contact tracing phases, including case identification, contacts identification and rapid exposure notification, surveillance, regular follow up and prevention. In addition, there is a phase of preparation and post-pandemic services for current and needed future technology that will aid in the fight against any incoming infectious diseases.
GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial
Authors: Irina R. Strambu, Christian A. Seemayer, Liesbeth M-C.A. Fagard, Paul A. Ford, Tom A.K. Van der Aa, Angela A. de Haas-Amatsaleh, Vikas Modgill, Eva Santermans, Eric N. Sondag, Eric G. Helmer, Toby M. Maher, Ulrich Costabel, Vincent Cottin
Journal: European Respiratory Journal (2022)

GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF).PINTA (ClinicalTrials.gov: NCT03725852) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance.In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was -33.68 (95% CI -112.0-44.68) mL with GLPG1205 and -76.00 (95% CI -170.7-18.71) mL with placebo (least squares mean difference 42.33 (95% CI -81.84-166.5) mL; p=0.50). Lung volumes by imaging declined -58.30 versus -262.72 mL (whole lung) and -33.68 versus -135.48 mL (lower lobes) with GLPG1205 versus placebo, respectively. Treatment with GLPG1205 versus placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib.Treatment with GLPG1205 did not result in a significant difference in FVC decline versus placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.
Correction: Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
Authors: Qingyi Ma, Zhen Zhao, Abhay P. Sagare, Yingxi Wu, Min Wang, Nelly Chuqui Owens, Philip B. Verghese, Joachim Herz, David M. Holtzman, Berislav V. Zlokovic
Journal: Molecular Neurodegeneration (2022)
Reversing “Flip-Flop” Phenomenon of 131I and Glucose Avidity in RET-Fusion Positive Radioiodine-Refractory Thyroid Cancer Lesions After Treatment of Pralsetinib
Authors: Hung-Pin Chan, I-Feng Chen, Fu-Ren Tsai, Chun-Hao Kao, Daniel Hueng-Yuan Shen
Journal: Clinical Nuclear Medicine (2022)

A 61-year-old man presented with papillary thyroid cancer in radioiodine-refractory status after high-activity 131 I treatments following thyroidectomy. FDG-avid neck and pulmonary metastases but without 131 I-uptake were detected. CCDC6-RET fusion was identified from the tumor lesion. He was treated with pralsetinib, a RET inhibitor, followed by another high-activity 131 I therapy. Posttherapeutic scan displayed restoration of 131 I avidity at those lesions only shown on previous FDG PET/CT. Reduced FDG avidity of those lesions and decreased serum antithyroglobulin antibody titer were also noticed. This case illustrated successfully reinduced 131 I avidity in papillary thyroid cancer through redifferentiation with target therapy to suppress tumor RET overexpression.
Immune Biomarkers in the Peripheral Blood and Tumor Microenvironment of Classical Hodgkin Lymphoma Patients in Relation to Tumor Burden and Response to Treatment
Authors: Tom A. Mulder, Maria L. Andersson, Lucía Peña-Pérez, Kia Heimersson, Ioanna Xagoraris, Björn E. Wahlin, Robert Månsson, Lotta Hansson, Georgios Rassidakis, Marzia Palma
Journal: HemaSphere (2022)

In classical Hodgkin lymphoma (cHL), the malignant cells represent only a small fraction of the tumor. Yet, they orchestrate a lymphocyte-dominated tumor microenvironment (TME) that supports their survival and growth. The systemic effects of this local immunomodulation are not fully elucidated. Here, we aimed at characterizing circulating lymphocytes and plasma proteins in relation to clinical parameters and treatment effect. Peripheral blood (PB) samples were obtained from 48 consecutive patients at diagnosis and at 2 time points after successful primary treatment. Single-cell suspensions were prepared from lymph node (LN) biopsies obtained for routine diagnostic purposes. Twenty healthy individuals were included as controls. Cells from PB and LN were analyzed by flow cytometry, and plasma proteins by Proximity Extension Assay. We found that the frequencies of T and B cells positively correlated between the LN and the PB compartments. Compared to controls, cHL patients had higher frequencies of proliferating T cells as well as higher expression of programmed death (PD)-1 and cytotoxic T lymphocyte antigen (CTLA)-4 in circulating T cells, and lower naive T-cell frequencies. Advanced-stage patients had fewer NK cells with a functionally impaired phenotype. Differences in the immune profile were observed in patients with a high tumor burden and with high inflammation, respectively. Most of these deviations disappeared after standard first-line treatment. Patients who received radiotherapy involving the mediastinum had low T-cell counts for a prolonged period. Our findings suggest that the immunomodulation of lymphocytes in the TME of cHL might affect immune biomarkers in the PB.
Re: Resolution of Misleading COVID-19 Vaccination-Related Nodal and Splenic FDG Uptake
Authors: Rujittika Mungmunpuntipantip, Viroj Wiwanitkit
Journal: Clinical Nuclear Medicine (2022)

∗Private Academic Consultant Bangkok, Thailand [email protected] †Honorary Professor Dr D.Y. Patil University Pune, India Conflicts of interest and sources of funding: none declared.
Empagliflozin in Patients with Chronic Kidney Disease
Authors: William G Herrington, Natalie Staplin, Christoph Wanner, Jennifer B Green, Sibylle J Hauske, Jonathan R Emberson, David Preiss, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Emily Sammons, Doreen Zhu, Michael Hill, Will Stevens, Karl Wallendszus, Susanne Brenner, Alfred K Cheung, Zhi-Hong Liu, Jing Li, Lai Seong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Aldo P Maggioni, Roberto Pontremoli, Rajat Deo, Shinya Goto, Xavier Rossello, Katherine R Tuttle, Dominik Steubl, Michaela Petrini, Dan Massey, Jens Eilbracht, Martina Brueckmann, Martin J Landray, Colin Baigent, Richard Haynes
Journal: New England Journal of Medicine (2022)

The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.
Where Are All the Women in Industry Advisory Boards?
Authors: Rachna T. Shroff, Karyn A. Goodman, Janice M. Mehnert, Julie M. Vose, Susan E. Moran, Jennifer L. Yessaian, Lance Baldo, Brian M. Alexander, Quita B. Highsmith, Jennifer M. Mills, Pamela L. Kunz
Journal: Journal of Clinical Oncology (2022)

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Engineered upconversion nanocarriers for synergistic breast cancer imaging and therapy: Current state of art
Authors: Pavan Kumar Chintamaneni, Dasari Nagasen, Katta Chanti Babu, Atul Mourya, Jitender Madan, Dadi A. Srinivasarao, R.K. Ramachandra, P. Madhuri Santhoshi, Sai Kiran S.S. Pindiprolu
Journal: Journal of Controlled Release (2022)
Exploring the Next Frontier in Non–Small-Cell Lung Cancer With High MET and Mutated Epidermal Growth Factor Receptor
Authors: Martin Sattler, Ravi Salgia
Journal: Journal of Clinical Oncology (2022)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein–Expressing Non–Small-Cell Lung Cancer. October 26, 2022 ARTICLE CITATION DOI: 10.1200/JCO.22.02086 Journal of Clinical Oncology - published online before print November 3, 2022 PMID: 36331252 Exploring the Next Frontier in Non–Small-Cell Lung Cancer With High MET and Mutated Epidermal Growth Factor Receptor Martin Sattler , PhD1,2xMartin SattlerSearch for articles by this author and Ravi Salgia , MD, PhD3xRavi SalgiaSearch for articles by this author Show More 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA2Department of Medicine, Harvard Medical School, Boston, MA3Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA https://doi.org/10.1200/JCO.22.02086 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologyAUTHOR CONTRIBUTIONSConception and design: All authorsManuscript writing: All authorsFinal approval of manuscript: All authorsAccountable for all aspects of the work: All authorsAUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTExploring the Next Frontier in Non–Small-Cell Lung Cancer With High MET and Mutated Epidermal Growth Factor ReceptorThe following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Ravi SalgiaConsulting or Advisory Role: Iovance Biotherapeutics, AbbVie, Novartis, AstraZenecaSpeakers' Bureau: AstraZeneca, MerckNo other potential conflicts of interest were reported. Companion Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein–Expressing Non–Small-Cell Lung Cancer